Prostate Carcinoma Research Articles

The Diagnostic Trap: When PSA Results Mislead. A Case Report.

Introduction: Immunoassays used in clinical practice can occasionally yield falsely elevated or suppressed results due to assay interference. We present a patient case of metastatic prostate cancer where plasma prostate-specific antigen (PSA) concentrations were falsely low. This was discovered incidentally, when a different laboratory, using another PSA assay, reported significantly higher values. Case presentation: A 77-year old man, diagnosed with prostate adenocarcinoma in 2011, developed bone metastases in 2015 and metastatic castration-resistant prostate cancer (mCRPC) in 2016. Between 2016 and 2017, PSA measurements at a different hospital using the Roche Cobas e602 assay, showed significantly higher plasma PSA concentrations compared to those measured at the initial hospital, using the Abbott Architect assay. Due to this discrepancy, which was inconsistent with the patient’s clinical status, the clinician contacted the laboratory. Subsequent investigation revealed an assay interference leading to falsely low PSA results with the Abbott Architect Assay. Conclusion: This case underscores the importance of close collaboration between clinicians and laboratories, as well as the need to consider analytical interference when clinical findings do not match laboratory results. Laboratories must continue working with assay manufacturers to minimize interference risks, and clinicians should remain vigilant for potential diagnostic pitfalls and consult the laboratory when inconsistencies arise.

Investigating the clinical significance of E2F5 expression in circulating extracellular vesicles in prostate carcinoma.

Prostate-specific antigen (PSA) based screening strategy has caused a marked improvement in prostate cancer detection and reduction in associated mortality. However, its specificity and sensitivity is not optimal for differentiating different forms of prostate cancer, resulting in overtreatment of indolent tumors. E2F5, a member of the family of transcription factors plays essential roles during many cellular processes. E2F5 amplification is a major event in PCa. A liquid biopsy is a minimally invasive procedure to investigate the cancer-related molecules in circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles (EVs). Serum and plasma are attractive sources of EV-based biomarkers as blood sample acquisition is a minimally invasive procedure. Given, the shortcomings of PSA as a serum marker, the suitability of E2F5 expression and chemical properties of EVs can be used for the diagnosis of clinically significant prostate cancer. To technically refine the current histopathology-based diagnosis of PCa by adding it to the molecular readouts specific to disease states and biochemical fingerprints of EVs. The study included 100 TRUS-biopsied tissues, 50 representing 4 Gleason grades and another 50 representing BPH. Expression of E2F5 was studied in all the qualified tissues by Immunohistochemistry (IHC). Blood from patients was collected and EVs were isolated and characterized. E2F5 was highly upregulated through all Gleason grades, the maximum being in Gleason 10(5 + 5) and the minimum in Gleason 7(3 + 4), as compared to BPH. The EVs isolated from blood plasma were within 30-200 nm in size. E2F5, being a transcription factor, is highly overexpressed in malignant biopsy tissues, through all Gleason grades. BPH tissues served as control samples. EVs from blood plasma might serve as a potential liquid biopsy marker for predicting disease progression and better prognosis.

FDG PET/CT in 2 Cases of Primary Urothelial Carcinoma of the Prostate.

Primary prostatic urothelial carcinoma is a very rare aggressive tumor with poor prognosis. We describe FDG PET/CT findings in 2 patients with primary prostatic urothelial carcinoma. In 1 patient, FDG PET/CT showed intense activity of the prostate tumor with extraprostatic invasion. In the other patient, FDG PET/CT showed heterogeneous intense activity of the primary tumor and multiple hypermetabolic metastases in the regional lymph nodes, bone, and lung. Both patients had normal serum total prostate-specific antigen levels. These cases highlight the usefulness of FDG PET/CT in detecting and staging of primary prostatic urothelial carcinoma due to high FDG avidity.

Comparative Study of Gleason 7 (3+4) and (4+3) Prostatic Adenocarcinomas with Prognostic Criteria and Immunohistochemical Profiles of AMACR, PSA and Ki-67.

To compare Gleason 7 (3+4) and (4+3) prostatic adenocarcinoma (PC) with different prognostic criteria through immunohistochemical analysis with anti-PSA, anti-Ki 67 and anti-AMARC antibodies. We analyzed 221 surgical specimens from patients between 40 and 86 years-old (mean=63) with PC. The immunohistochemical study was performed with anti-PSA, anti-Ki 67 and anti-AMARC. The microscopic fields were photographed with an Olympus DP70 digital camera coupled to an Olympus BX51 microscope and archived in TIFF. Proportion and intensity criteria were used to quantify the anti-PSA antibody and for the anti-Ki 67 antibody, the quantification by similarity of this antibody in breast carcinomas. Anti-AMACR protein expression was based on four scores: negative, weak, moderate and strong. The statistical analysis was performed with the Graph Pad Prism 5 program. In the Gleason score 7 (3+4) we had 91.72% in pT2 and 8.27% in the pT3 group; 8.27% recurrences, of which 90.90% in the pT2 group. In the Gleason score 7 (4+3) we had 77.27% in the pT2 group and 22.72% in the pT3 group and 10.22% of relapses, of which 66.66% in the pT2 group and 33.33% in the pT3 group. In 6.81% of cases there was an increase in the anti-Ki 67 index and in 2.27% of the cases, there was an increase in the immunoexpression of anti-p53 when comparing Gleason score 7 (3+4) with Gleason score 7 (4+3). Our study confirmed differences in the Gleason score 7 (3+4) and Gleason score 7 (4+3) of PC when comparing prognostic criteria. Anti-Ki 67 and anti-PSA antibody immunostaining showed a positive correlation as the Gleason score 7 increased from (3+4) to (4+3).

Challenges and Clinical Relevance in Diagnosing Metastatic Cells From Non-Hematopoietic Malignancies in Bone Marrow Aspirates.

The causes of cytopenias are numerous, and the bone marrow aspirate helps to identify them. In rare cases, these cytopenias are due to bone marrow metastases from solid cancers. The techniques used in hematology laboratories are limited in characterizing these cells. Interaction with the cytopathology laboratory becomes critical for characterizing tumor cells and completing a comprehensive diagnosis from the bone marrow aspirate. This article describes a series of 38 bone marrow aspirates from 36 patients with bicytopenias who underwent bone marrow aspiration and for whom the hematologists sent the sample to the cytopathology laboratory to complete the diagnosis by immunocytochemistry and FISH if necessary. The mean age of patients is 66 years, and the sex ratio is 2.8. Metastases were found in 11 cases of lung carcinoma, 4 cases of prostate carcinoma, 2 cases of breast carcinoma, 1 case of kidney carcinoma, 1 case of glioblastoma, 1 case of Ewing's sarcoma, and 1 case of melanoma. Among them, bone marrow aspiration was the only method to establish the initial diagnosis for seven patients. In six cases, immunocytochemistry confirmed the presence of carcinoma cells but could not identify their origin. In seven cases, tumor cells were insufficient to be characterized by immunocytochemistry. Collaboration between laboratories is essential for the management of bone marrow aspirates containing non-hematopoietic metastases. Bone marrow aspiration may be sufficient to diagnose solid tumors, enabling faster initiation of treatment for patients already at an advanced stage of their disease.

New Difunctional Derivatives of Betulin: Preparation, Characterization and Antiproliferative Potential

Biologically active compounds of natural origin, such as betulin, are a source of obtaining new medicinal substances. The presence of chemically active hydroxyl groups in the betulin structure at C-3 and C-28 positions enables esterification with dicarboxylic acid anhydrides or carboxylic acids. As a result of a four-step synthesis, difunctional betulin derivatives were obtained, which were evaluated for their antiproliferative activity against the following human cell lines: leukemia (MV4-11), (A549), breast cancer (MCF-7), prostate adenocarcinoma (PC-3), colon cancer (HCT116), pancreatic cancer (MiaPaca-2), and melanoma (Hs294T). The target 3-carboxyacyl-28-alkynyloyl betulin derivatives showed significant antiproliferative activity against MV4-11 cells. For 3-carboxyacylbetulins and their selected alkynyl derivatives, studies to investigate the effect on the cell cycle and apoptosis process, as well as drug similarity analysis, were performed.

Prognosis of Gleason 7 (3+4) prostatic adenocarcinoma with a low rate of grade 4 - Retrospective study of 104 cases

The aim of this study was to compare the prognosis of Gleason Score (GS) 7 (3+4) prostatic adenocarcinoma with a low percentage of grade 4 to that of GS6 (3+3) prostatic adenocarcinoma. All patients with GS6 or GS7 prostatic adenocarcinoma who underwent prostatectomy between 2014 and 2018 were selected. The prostate biopsy (PB) and prostatectomy resection specimen (RS) slides were reviewed by 2 pathologists. A statistical analysis was carried out to evaluate the relationship between the clinical, paraclinical and histological characteristics of the patients on biopsies and prostatectomies with the risk of recurrence. One hundred and four patients were included. A recurrence occurred in 21 patients (20.2%). In univariate analysis, an association was observed between the risk of recurrence and the GS (P=0.014 for PB / P=0.006 for RS), grade 4 percentage (P=0.020/P=0.002), especially by applying the thresholds of 5% (P=0.008/P=0.018) and 10% (P=0.015/P<0.001), the tumor stage pT (P=0.045), the quality of surgical resection R (P=0.015) and the size of the tumor focus in contact with the limits (P<0.001). In multivariate analysis, grade 4 percentage greater than 10% was associated with the risk of recurrence on biopsy and prostatectomy (respectively OR 4.83 [IC95 1.38; 16.88]; P=0.014 and OR 6.29 [IC95 1.96; 20.20]; P=0.002), as well as R1 resection (OR 3.65 [IC95 1.24; 10.76]; P=0.019 and OR 4.06 [IC95 1.27; 13.03]; P=0.018). Our study suggests that GS7 (3+4) tumors with less than 10% of grade 4 have a similar prognosis to that of GS6 (3+3) tumors. This could allow some GS7 (3+4) patients to benefit from the active surveillance therapy, instead of undergoing more aggressive treatments such as surgery or radiotherapy.

Oxidative stress-associated gene signature predicts the prognosis and therapy response in prostate adenocarcinoma

Background: Oxidative stress contributes to the development of prostate adenocarcinoma (PRAD). However, the prognosis prediction and therapy response predicted based on oxidative stress-associated genes lacked comprehensive study. Herein, an integrated bioinformatics approach was adopted to identify the prognosis-associated oxidative stress genes for PRAD. Methods: From Gene-Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, the transcriptomic data and clinical data were collected. Genes related to oxidative stress were retrieved from oxidative stress pathway "GOBP_RESPONSE_TO_OXIDATIVE_STRESS" in the MsigDB. A risk model was constructed based on the hub genes selected by both WGCNA analysis and LASSO analysis. GEO cohort was used for verifying the model robustness. By running CIBERSORT and ESTIMATE algorithm, immune cell infiltration was quantified. TIDE algorithm and Spearman correlation analysis were used for evaluating the immunotherapy response and drug sensitivity. RT-qPCR analysis and CCK-8 were carried out to validate the results. Results: We established oxidative stress-related gene signature (NUDT7, NTRK3, MAP3K12, DRD5, C3orf18, and B3GALT2) as an independent factor for the prognostic survival of PRAD. In virto experiments showed that MAP3K12 had a higher expression in PRAD cell lines, and knockdown of MAP3K12 inhibited PC3 cell viability. The risk score was positively linked with T_ cells_ regulatory_ Tregs and Macrophages_ M2 and negatively linked with Plasma_cells. High-risk patients showed higher expressions of PDCD1, CD274, CTLA4, LAG3, PDCDILG2, BTLA, HAVCR2, TIGIT, and higher myeloid-derived suppressor (MDSC) score. Docetaxel, Cisplatin, and Bicalutamide could benefit low-risk patients more. Calibration curves and DCA showed an accurate prediction by the nomogram. Conclusion: We established a novel and reliable prognostic model for PRAD patients.

An Integrated Approach Utilizing Single-Cell and Bulk RNA-Sequencing for the Identification of a Mitophagy-Associated Genes Signature: Implications for Prognostication and Therapeutic Stratification in Prostate Cancer

Introduction: Prostate cancer, notably prostate adenocarcinoma (PARD), has high incidence and mortality rates. Although typically resistant to immunotherapy, recent studies have found immune targets for prostate cancer. Stratifying patients by molecular subtypes may identify those who could benefit from immunotherapy. Methods: We used single-cell and bulk RNA sequencing data from GEO and TCGA databases. We characterized the tumor microenvironment at the single-cell level, analyzing cell interactions and identifying fibroblasts linked to mitophagy. Target genes were narrowed down at the bulk transcriptome level to construct a PARD prognosis prediction nomogram. Unsupervised consensus clustering classified PARD into subtypes, analyzing differences in clinical features, immune infiltration, and immunotherapy. Furthermore, the cellular functions of the genes of interest were verified in vitro. Results: We identified ten cell types and 160 mitophagy-related single-cell differentially expressed genes (MR-scDEGs). Strong interactions were observed between fibroblasts, endothelial cells, CD8+ T cells, and NK cells. Fibroblasts linked to mitophagy were divided into six subtypes. Intersection of DEGs from three bulk datasets with MR-scDEGs identified 26 key genes clustered into two subgroups. COX regression analysis identified seven prognostic key genes, enabling a prognostic nomogram model. High and low-risk groups showed significant differences in clinical features, immune infiltration, immunotherapy, and drug sensitivity. In prostate cancer cell lines, CAV1, PALLD, and ITGB8 are upregulated, while CLDN7 is downregulated. Knockdown of PALLD significantly inhibits the proliferation and colony-forming ability of PC3 and DU145 cells, suggesting the important roles of this gene in prostate cancer progression. Conclusions: This study analyzed mitophagy-related genes in PARD, predicting prognosis and aiding in subtype identification and immunotherapy response analysis. This approach offers new strategies for treating prostate cancer with specific molecular subtypes and helps develop potential biomarkers for personalized medicine strategies.

XCT as a potential marker for neuroendocrine cells in high-risk prostate cancer and the relation to AL122023.1-miR-26a/30d/30e axis.

Prostate cancer is the second most common type of cancer in male worldwide. Stromal-epithelial interaction is thought to have a major impact on cancer development and progression. Previous studies have shown that interaction via soluble factors lead to a reduction in the expression of xCT and AL122023.1 in the prostate carcinoma cell line LNCaP after seven days of co-culture with primary stromal p21 cells. In this study, we validated the repression of xCT and AL122023.1 at RNA level using quantitative real-time PCR and at protein level by Western Blotting. Furthermore, xCT is known to be a putative target for miRNAs miR-26a, miR-30d and miR-30e, which in turn potentially interact with AL122023.1. The lncRNA-miRNA-interaction was verified by luciferase reporter assays. However, miR-26a/-30d/-30e did not inhibit xCT expression at protein level. Nevertheless, indirect inhibitory effect of AL122023.1 on the xCT expression could be shown. Moreover, immunostaining revealed precise xCT expression in neuroendocrine cells, ranging from fetal, healthy juvenile, and adult prostate tissue to benign prostatic hyperplasia and finally advanced prostate cancer. This study explores the relevance and function of xCT and AL122023.1 in the prostate and exposes xCT as a potential marker or therapeutic target in high-risk prostate cancer.

Abstract A005: 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics

Abstract Objective: PARP (poly [ADP-ribose] polymerase) inhibitors are approved for a variety of malignancies including those with a breast, prostate, and ovarian carcinoma, particularly in the setting of a germline or somatic pathogenic BRCA mutation. There is active interest in the development of theranostics including those with a PARP inhibitor backbone. Methods: We evaluate a novel PARP inhibitor (PARPi) PET tracer 18-Fluorine [18F] Fluorthanatrace (FTT). Patients with primary or metastatic solid tumors with measurable disease initiating therapy with a PARP inhibitor monotherapy or in combination with another systemic agent were eligible. Patients underwent 18F-FTT PET/CT prior to initiation of PARPi and a second 18F-FTT PET 2-4 weeks after initiation of a PARP inhibitor. Hematologic toxicity on PARPi monotherapy or combination was assessed using the CTCAEv5.0 criteria. Regions of interest were drawn over the uninvolved bone marrow (usually taken at L3) and normal muscle to obtain the maximum standardized uptake value. Bone marrow to muscle ratio (B/M) was calculated at baseline and on PARPi. Spearman rank correlation coefficient was used. Results: A total of 21 patients were enrolled and underwent 18F-FTT PET. Patients had a median of 0 (range 0-7) prior lines of systemic therapy. The primary disease site included breast (9), ovary (6), primary peritoneal (1), pancreas (1)and other (4). Measurable uptake of 18F-FTT within the tumor and bone marrow was observed in all patients. Median L3 SUVmax at baseline was 4.3 (range 2.1-11.8) vs. 2.33 (range 1.4-2.9) while on PARP inhibitor. Baseline B/M was associated with highest grade hematologic toxicity in patients (n=10) who received talazoparib monotherapy or combination (r=0.65, p=0.042). While B/M was not associated with hematologic toxicity in patients (n=11) who received olaparib monotherapy or combination (r=0.098, p=0.77). Conclusions: 18F-FTT PET can measure target engagement of PARP inhibitors in bone marrow and may have implications for PARP inhibitor-based theranostics and dosing. Results suggest there may be differential impact of different PARPi on bone marrow and should be considered when selecting a backbone for theranostics. Citation Format: Lilie Lin, Mahmoud Hammad, Franklin Wong, Timothy A. Yap. 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A005.

Polyomavirus infection in urological cancers: role of SV40, BKPyV, and JCPyV in prostate, bladder, and renal carcinomas

Polyomavirus infection in urological cancers: role of SV40, BKPyV, and JCPyV in prostate, bladder, and renal carcinomas

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer. Expression of the lncRNA BOLA3-DT was analyzed between normal and tumor samples in the GDC TCGA PRAD (Genomic Data Commons: The Cancer Genome Atlas Prostate Adenocarcinoma Collection) dataset. Disease progression-related clinicopathological parameters such as serum PSA level (ng/ml) and Gleason score were associated with the expression of BOLA3-DT using the same GDC TCGA PRAD dataset. To validate these findings, the expression of BOLA3-DT was checked in our sample set of 15 PCa (prostate cancer) and 15 BPH (benign hypertrophy of the prostate) patients. In the GDC TCGA PRAD dataset, the expression of the lncRNA BOLA3-DT was significantly downregulated in prostate cancer tissue samples (n = 492) compared to adjacent normal (n = 52; p < 0.0001), and, there was a significant negative correlation between the expression of the lncRNA BOLA3-DT and the serum PSA level (p < 0.01). However, no significant association was found between the lncRNA BOLA3-DT expression and the Gleason score (p > 0.05). In this study, it was found that BOLA3-DT was downregulated in PCa tissue samples compared to BPH samples (p > 0.05). In the GDC TCGA PRAD dataset, it was revealed that BOLA3-DT could serve as an excellent diagnostic marker with a sensitivity of 86.9% and a specificity of 84.6% (AUC-0.916). LncRNA BOLA3-DT, a novel long non-coding RNA, was found to be downregulated in prostate cancer. The expression of the lncRNA BOLA3-DT can serve as a diagnostic marker in prostate cancer.

P1073 Clinical characteristics and outcomes of patients with Inflammatory Bowel Disease under long term (&amp;gt;10years) anti-TNFa treatment

Abstract Background There is limited information in the literature regarding long term effectiveness and safety of anti-TNFa agents in patients with Inflammatory Bowel Disease (IBD). We aimed to study the effectiveness and safety of anti-TNFa agents in IBD patients receiving this treatment beyond 10 years . Methods Consecutive IBD patients under anti-TNFa treatment &amp;gt;10 years were prospectively studied. Demographic and clinical characteristics as well as treatment details and outcomes were recorded based on an updated IBD registry. Outcomes included need for treatment optimization [dose escalation or immunosuppressant (IMM) addition], disease related hospitalizations and surgeries, serious infections and malignancies. Drug survival of anti-TNF treatment &amp;gt;10 years was assessed (at 13 and 15 years). Results Out of 395 patients being initiated with any anti-TNFa in our department, 56 with at least 10 years of anti-TNFa use [males 32(57%), mean age (±SD) 53.3(±13) years, mean disease duration (±SD) 22.8 (±1.15) years were included. Patients were 82%(46/56) with CD, mean duration of anti-TNFa use (±SD) 162 (±32.93) months, 39 (70%) under infliximab, 17 under adalimumab, while anti-TNFa represented the first biologic in 88% of them. More than half of the patients [54%(30/56)] were under combination treatment with IMM (24 azathioprine, 6 methotrexate) and 45% (25/56) needed dose escalation. During follow up 75% (42/56) remained on the index anti-TNFa, precisely 84% (31/37) at 13 and 55% (16/29) at 15 years after drug initiation respectively (figure 1). Main causes of discontinuation were loss of response (8/14), patient preference 1, malignancy 2, osteonecrosis 1, death of other cause 1 and deep remission 1. During follow up, a total of 30 disease related hospitalizations in 18 patients, 12 serious infections, 6 malignancies (non Hodgkin lymphoma of the liver, prostate carcinoma, thyroid gland carcinoma, hepatocellular carcinoma and two cases of non melanoma skin cancer) and 4 disease related operations were recorded. Conclusion More than half of the patients under long-term anti-TNFa treatment (&amp;gt;10 years) continue to receive the agent for an additional 5 years. Rates of serious infections and malignancies are no negligible and close monitoring is needed in these patients.

Use of Relugolix for the Prevention of Impending Oliguria and Progressive Renal Failure in a Suspected Case of Prostate Carcinoma

Use of Relugolix for the Prevention of Impending Oliguria and Progressive Renal Failure in a Suspected Case of Prostate Carcinoma

Full Disappearance of PC3‐Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes

AbstractIron oxide nanoparticles have been proposed for magnetic hyperthermia treatment of tumors. However, efficacy depends on the injection of large amounts of such nanoparticles and the equipment is costly. Here, a new thermal cancer treatment is described, in which a tumor containing a low concentration of nonpyrogenic pure iron oxide nanominerals coated with carboxy‐methyl‐dextran (M‐CMD), corresponding to modified magnetosomes, are exposed to ultrasound. Heating PC3 prostate carcinoma cells between 43 and 46°C using ultrasound in the presence of M‐CMD resulted in significant necrotic cell death. Furthermore, deposition of M‐CMD containing 3 µg of iron per mm3 of tumor in subcutaneous xenografts of PC3‐Luc tumors of 150 mm3 followed by 6 to 10 sessions of ultrasound application (1 W cm−2, 1 MHz) of 10 min each led to a tumor temperature of 43–46°C per session and to total tumor disappearance without regrowth over 6 months following treatment start. Sequential histological analyses of the tumor tissues revealed partial tumor occupation by M‐CMD and an increase in cell death over time. Neither lesions, nor magnetosome accumulation were found in microscopic sections of various internal organs collected from treated mice euthanized 6 months after the beginning of the treatment, indicating that M‐CMD may not lead to long‐term side effects.

IL-1β in Neoplastic Disease and the Role of Its Tumor-Derived Form in the Progression and Treatment of Metastatic Prostate Cancer.

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β synthesized and secreted by immune cells. Herein, we discuss the importance of IL-1β derived from cancer cells which impacts primary tumors, particularly metastatic lesions, separately from and in addition to its more recognized role in immune-mediated inflammatory events. To this end, we focus on the instrumental contribution of IL-1β in the establishment and progression of advanced prostate adenocarcinoma. Special emphasis is placed on the potential role that the standard-of-care treatment strategies for prostate cancer patients have in unleashing IL-1β expression and production at metastatic sites. We conclude by reviewing the therapeutics currently used for blocking IL-1β signaling and propose a rationale for their concomitant use with standard-of-care treatments to improve the clinical outcomes of advanced prostate cancer.

Feasibility and safety of Taipei Veterans General Hospital Heavy Ion Therapy Center: The first carbon-ion irradiation facility in Taiwan.

Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan. Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE)). During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease. Carbon-ion radiotherapy was determined to be an effective and safe treatment.

Emergence of Neuroendocrine Tumors in Patients Treated with Androgen Receptor Pathway Inhibitors for Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.

It has been shown that androgen receptor pathway inhibitor (ARPIs) treatment for metastatic castration-resistant prostate cancer (mCRPC) improves overall survival rates, but ARPIs appear to be associated with a higher frequency of treatment-related neuroendocrine prostate cancer (t-NEPC). Our aim was to quantify the proportion of prostate adenocarcinoma cases that transition to t-NEPC following ARPI therapy. We conducted a comprehensive search of the literature on t-NEPC using databases including MEDLINE and Scopus. Eligible studies reported outcome data for NEPC in patients with prior mCRPC treated with an ARPI. To determine the pooled frequency of neuroendocrine transformation, the Freeman-Tukey variance-stabilizing arcsine transformation was applied to individual frequencies. Among the 938 patients in eight eligible studies, t-NEPC diagnosis was confirmed in 171 patients, predominantly via pathology. Baseline biopsy verification to ensure the absence of NEPC was performed in most cases. The definition of t-NEPC varied among the studies. Five studies used a morphological definition based on histopathology, and three studies used NEPC biomarker detection on circulating tumor cells. A meta-analysis of aggregate data revealed an overall NEPC frequency following ARPI therapy of 16% (95% confidence interval 9-24%). ARPI-related NEPC represents a frequently underdiagnosed late complication of mCRPC. Given the absence of biomarkers for diagnosis, routine repeat biopsy at the mCRPC stage should be considered to diagnose t-NEPC transitions.

Comparing the effectiveness of digital rectal examination, prostate specific antigen, and TRUS guided prostate biopsy, in the detection of prostate cancer

Prostate cancer has been the most common malignancy in men accounting for one fourth of cancers. Use of Trans rectal ultrasonography (TRUS) in men with an abnormal PSA and/or digital rectal examination acting as a guide to direct prostate biopsies will lead to decrease in number of early deaths It is a prospective observational study.All the patients attending the Urology Out patient Department with a suspicion of Ca prostate from clinical signs and symptoms were clinically evaluated using Digital Rectal Examination and screened for serum PSA levels. All the patients in whom abnormality was detected on DRE and/or an elevated serum PSA level were included in the study and TRUS biopsy was done. The statistical analysis was executed by SPSS version 20 continuous variables were analyzed with student t -test. The present study includes 95 men in whom abnormality detected in DRE or in the levels of serum PSA.10 core biopsy was done in 53 patients and 16 core biopsy was done in 42 patients. Among the total number of patients subjected to TRUS guided prostate biopsy either 10 core or 16 core, 31 patients detected with prostatic adenocarcinoma which accounts for 32.6%, 12 patients had High grade PIN accounting for 12.62%, 30 patients (31.57%) detected with fibroadenoleiomyomatous hyper plasia , 5 patients had fibroadenoleiomyomatous hyperplasia with chronic prostatitis which is 5.20% and chronic prostatitis is found in 15 patients attributing to 15.78%.Cancer detection rate with abnormalities in PSA alone was found to be 15% while it was 70% when both DRE and PSA showed abnormal results which is significantly higher. It shows that both DRE and PSA has to be considered while estimating the cancer rate. Detection rate with 16 core TRUS guided biopsy is 54.76% which is significantly (P value 0.0037) higher than that of 10 core biopsy (15.09 %).